Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Biochemical Pharmacology

Volumn 79, Issue 2, 2010, Pages 77-89

  Buffo, Annalisa ^a   Rolando, Chiara ^a   Ceruti, Stefania ^b  

^a UNIVERSITY OF TURIN   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

Author keywords

Brain repair; Cytokines; Extracellular nucleotides; Glial scar; Neural stem cells; Reactive astrogliosis

Indexed keywords

ADENINE NUCLEOTIDE; ADENOSINE; ADENOSINE TRIPHOSPHATE; BRAIN DERIVED NEUROTROPHIC FACTOR; CYCLOOXYGENASE 2; CYTOKINE; EPIDERMAL GROWTH FACTOR; GAMMA INTERFERON; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GROWTH FACTOR; GUANOSINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; NEUROTROPHIN 3; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; PURINE; PURINERGIC P2X RECEPTOR; PURINERGIC P2Y RECEPTOR; PYRIMIDINE; TRANSCRIPTION FACTOR NFAT; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

ARTICLE; ASTROCYTE; ASTROCYTOSIS; BLOOD BRAIN BARRIER; BRAIN DAMAGE; CELL ACTIVATION; CELL DAMAGE; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; CYTOKINE RELEASE; GENE AMPLIFICATION; GLIA; HUMAN; MACROGLIA; MOLECULAR MECHANICS; NERVE CELL PLASTICITY; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TARGET CELL; TISSUE REGENERATION; TISSUE REPAIR; UPREGULATION;

ASTROCYTES; BRAIN; BRAIN INJURIES; HUMANS;

EID: 71749103005     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2009.09.014     Document Type: Note

References (168)

1. Pekny M., and Nilsson M. Astrocyte activation and reactive gliosis. Glia 50 (2005) 427-434
2. Buffo A., Rite I., Tripathi P., Lepier A., Colak D., Horn A.-P., et al. Origin and progeny of reactive gliosis: a source of multipotent cells in the injured brain. Proc Natl Acad Sci USA 105 (2008) 3581-3586
3. Ridet J.L., Malhotra S.K., Privat A., and Gage F.H. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20 (1997) 570-577
4. Silver J., and Miller J.H. Regeneration beyond the glial scar. Nat Rev Neurosci 5 (2004) 146-156
5. Liberto C.M., Albrecht P.J., Herx L.M., Yong V.W., and Levison S.W. Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 89 (2004) 1092-1100
6. Abbracchio M.P., and Ceruti S. Role of P2 receptors in glial cells: focus on astrocytes. Purinergic Signal 2 (2006) 595-604
7. Vitellaro-Zuccarello L., Mazzetti S., Madaschi L., Bosisio P., Fontana E., Gorio A., et al. Chronic erythropoietin-mediated effects on the expression of astrocyte markers in a rat model of contusive spinal cord injury. Neuroscience 151 (2008) 452-466
8. de Bilbao F., Arsenijevic D., Moll T., Garcia-Gabay I., Vallet P., Langhans W., et al. In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice. J Neurochem 110 (2009) 12-22
9. Ito M., Natsume A., Takeuchi H., Shimato S., Ohno M., Wakabayashi T., et al. Type I interferon inhibits astrocytic gliosis and promotes functional recovery after Spinal Cord Injury by Deactivation of the MEK/ERK Pathway. J Neurotrauma 26 (2009) 41-53
10. Pascual O., Casper K.B., Kubera C., Zhang J., Revilla-Sanchez R., Sul J.Y., et al. Astrocytic purinergic signaling coordinates synaptic networks. Science 310 (2005) 113-116
11. Abbracchio M.P., Burnstock G., Boeynaems J.M., Barnard E.A., Boyer J.L., Kennedy C., et al. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58 (2006) 281-341
12. Kennedy C., McLaren G.J., Westfall T.D., and Sneddon P. ATP as a co-transmitter with noradrenaline in sympathetic nerves-function and fate. Ciba Found Symp 198 (1996) 223-235 [discussion 235-8]
13. Coco S., Calegari F., Pravettoni E., Pozzi D., Taverna E., Rosa P., et al. Storage and release of ATP from astrocytes in culture. J Biol Chem 278 (2003) 1354-1362
14. Lecca D., and Ceruti S. Uracil nucleotides: from metabolic intermediates to neuroprotection and neuroinflammation. Biochem Pharmacol 75 (2008) 1869-1881
15. Melani A., Turchi D., Vannucchi M.G., Cipriani S., Gianfriddo M., and Pedata F. ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochem Int 47 (2005) 442-448
16. Kreda S.M., Seminario-Vidal L., Heusden C., and Lazarowski E.R. Thrombin-promoted release of UDP-glucose from human astrocytoma cells. Br J Pharmacol 153 (2008) 1528-1537
17. Fumagalli M., Brambilla R., D'Ambrosi N., Volonté C., Matteoli M., Verderio C., et al. Nucleotide-mediated calcium signaling in rat cortical astrocytes: role of P2X and P2Y receptors. Glia 43 (2003) 218-223
18. Bolego C., Ceruti S., Brambilla R., Puglisi L., Cattabeni F., Burnstock G., et al. Characterization of the signalling pathways involved in ATP- and basic fibroblast growth factor-induced astrogliosis. Br J Pharmacol 121 (1997) 1692-1699
19. Brambilla R., Burnstock G., Bonazzi A., Ceruti S., Cattabeni F., and Abbracchio M.P. Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis. Br J Pharmacol 126 (1999) 563-567
20. Neary J.T., Kang Y., Bu Y., Yu E., Akong K., and Peters C.M. Mitogenic signaling by ATP/P2Y purinergic receptors in astrocytes: involvement of a calcium-independent protein kinase C, extracellular signal-regulated protein kinase pathway distinct from the phosphatidylinositol-specific phospholipase C/calcium pathway. J Neurosci 19 (1999) 4211-4220
21. Franke H., Krügel U., Schmidt R., Grosche J., Reichenbach A., and Illes P. P2 receptor-types involved in astrogliosis in vivo. Br J Pharmacol 134 (2001) 1180-1189
22. Brambilla R., Neary J.T., Cattabeni F., Cottini L., D'Ippolito G., Schiller P.C., et al. Induction of COX-2 and reactive gliosis by P2Y receptors in rat cortical astrocytes is dependent on ERK1/2 but independent of calcium signalling. J Neurochem 83 (2002) 1285-1296
23. Bagchi S., Liao Z., Gonzalez F.A., Chorna N.E., Seye C.I., Weisman G.A., et al. The P2Y2 nucleotide receptor interacts with alphav integrins to activate Go and induce cell migration. J Biol Chem 280 (2005) 39050-39057
24. Verkhratsky A., Krishtal O.A., and Burnstock G. Purinoceptors on neuroglia. Mol Neurobiol 39 (2009) 190-208
25. Di Virgilio F. Liaisons dangereuses: P2X(7) and the inflammasome. Trends Pharmacol Sci 28 (2007) 465-472
26. Fredholm B.B., IJzerman A.P., Jacobson K.A., Klotz K.N., and Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53 (2001) 527-552
27. Hindley S., Herman M.A., and Rathbone M.P. Stimulation of reactive astrogliosis in vivo by extracellular adenosine diphosphate or an adenosine A2 receptor agonist. J Neurosci Res 38 (1994) 399-406
28. 3 adenosine receptor mediates cell spreading, reorganization of actin cytoskeleton, and distribution of Bcl-XL: studies in human astroglioma cells. Biochem Biophys Res Commun 241 (1997) 297-304
29. Rathbone M., Pilutti L., Caciagli F., and Jiang S. Neurotrophic effects of extracellular guanosine. Nucleosides Nucleotides Nucleic Acids 27 (2008) 666-672
30. Hauwel M., Furon E., Canova C., Griffiths M., Neal J., and Gasque P. Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, "protective" glial stem cells and stromal ependymal cells. Brain Res Brain Res Rev 48 (2005) 220-233
31. Marchetti B., and Abbracchio M.P. To be or not to be (inflamed)-is that the question in anti-inflammatory drug therapy of neurodegenerative disorders?. Trends Pharmacol Sci 26 (2005) 517-525
32. Candelario-Jalil E., Yang Y., and Rosenberg G.A. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 158 (2009) 983-994
33. Lin H.W., Basu A., Druckman C., Cicchese M., Krady J.K., and Levison S.W. Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a penetrating brain injury. J Neuroinflammation 3 (2006) 15
34. Kordek R., Nerurkar V.R., Liberski P.P., Isaacson S., Yanagihara R., and Gajdusek D.C. Heightened expression of tumor necrosis factor alpha, interleukin 1 alpha, and glial fibrillary acidic protein in experimental Creutzfeldt-Jakob disease in mice. Proc Natl Acad Sci USA 93 (1996) 9754-9758
35. Swartz K.R., Liu F., Sewell D., Schochet T., Campbell I., Sandor M., et al. Interleukin-6 promotes post-traumatic healing in the central nervous system. Brain Res 896 (2001) 86-95
36. Campbell I.L. Cytokine-mediated inflammation and signaling in the intact central nervous system. Prog Brain Res 132 (2001) 481-498
37. Yong V.W., Moumdjian R., Yong F.P., Ruijs T.C., Freedman M.S., Cashman N., et al. Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc Natl Acad Sci USA 88 (1991) 7016-7020
38. Chiang C.S., Stalder A., Samimi A., and Campbell I.L. Reactive gliosis as a consequence of interleukin-6 expression in the brain: studies in transgenic mice. Dev Neurosci 16 (1994) 212-221
39. Giulian D., Woodward J., Young D.G., Krebs J.F., and Lachman L.B. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci 8 (1998) 2485-2490
40. Escartin C., Pierre K., Colin A., Brouillet E., Delzescaux T., Guillermier M., et al. Activation of Astrocytes by CNTF induces metabolic plasticity and increases resistance to metabolic insults. J Neurosci 27 (2007) 7094-7104
41. Kahn M.A., Huang C.J., Caruso A., Barresi V., Nazarian R., Condorelli D.F., et al. Ciliary neurotrophic factor activates JAK/Stat signal transduction cascade and induces transcriptional expression of glial fibrillary acidic protein in glial cells. J Neurochem 68 (1997) 1413-1423
42. Rabchevsky A.G., Weinitz J.M., Coulpier M., Fages C., Tinel M., and Junier M.P. Role for transforming growth factor-α as an inducer of astrogliosis 18 (1998) 10541-10552
43. Sharif A., Legendre P., Prevot V., Allet C., Romao L., Studler J.M., et al. Transforming growth factor alpha promotes sequential conversion of mature astrocytes into neural progenitors and stem cells. Oncogene 26 (2006) 2695-2706
44. Klein M.A., Möller J.C., Jones L.L., Bluethmann H., Kreutzberg G.W., and Raivich G. Impaired neuroglial activation in interleukin-6 deficient mice. Glia 19 (1997) 227-233
45. Martin A., Hofmann H.D., and Kirsch M. Glial reactivity in ciliary neurotrophic factor-deficient mice after optic nerve lesion. J Neurosci 23 (2003) 5416-5424
46. Wang D.D., and Bordey A. The astrocyte odyssey. Prog Neurobiol 86 (2008) 342-367
47. Schwartz J.P., and Nishiyama N. Neurotrophic factor gene expression in astrocytes during development and following injury. Brain Res Bull 35 (1994) 403-407
48. Chen L.W., Zhang J.P., Kwok-Yan Shum D., and Chan Y.S. Localization of nerve growth factor, neurotrophin-3, and glial cell line-derived neurotrophic factor in nestin-expressing reactive astrocytes in the caudate-putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/Bl mice. J Comp Neurol 497 (2006) 898-909
49. Papavassiliou E., Gogate N., Proescholdt M., Heiss J.D., Walbridge S., Edward, et al. Vascular endothelial growth factor (vascular permeability factor) expression in injured rat brain. J Neurosci Res 49 (1997) 451-460
50. Nieto-Sampedro M., and Bovolenta P. Growth factors and growth factor receptors in the hippocampus. Role in plasticity and response to injury. Prog Brain Res 83 (1990) 341-355
51. Smith C., Berry M., Clarke W.E., and Logan A. Differential expression of fibroblast growth factor-2 and fibroblast growth factor receptor 1 in a scarring and nonscarring model of CNS injury in the rat. Eur J Neurosci 13 (2001) 443-456
52. Messersmith D.J., Murtie J.C., Le T.Q., Frost E.E., and Armstrong R.C. Fibroblast growth factor 2 (FGF2) and FGF receptor expression in an experimental demyelinating disease with extensive remyelination. J Neurosci Res 62 (2000) 241-256
53. Hinks G.L., and Franklin R.J. Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta1 gene expression during remyelination of experimentally-induced spinal cord demyelination. Mol Cell Neurosci 14 (1999) 153-168
54. Scharr D.G., Sieber B.A., Dreyfus C.F., and Black I.B. Regional and cell-specific expression of GDNF in rat brain. Exp Neurol 124 (1993) 368-371
55. Brambilla R., Cottini L., Fumagalli M., Ceruti S., and Abbracchio M.P. Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes. Glia 43 (2003) 190-194
56. Liu B., Chen H., Johns T.G., and Neufeld A.H. Epidermal growth factor receptor activation: an upstream signal for transition of quiescent astrocytes into reactive astrocytes after neural injury. J Neurosci 26 (2006) 7532-7540
57. Codeluppi S., Svensson C.I., Hefferan M.P., Valencia F., Silldorff M.D., Oshiro M., et al. The Rheb mTOR pathway is upregulated in reactive astrocytes of the injured spinal cord. J Neurosci 29 (2009) 1093-1104
58. Ni W., Rajkumar K., Nagy J.I., and Murphy L.J. Impaired brain development and reduced astrocyte response to injury in transgenic mice expressing IGF binding protein-1. Brain Res 769 (1997) 97-107
59. Krum J.M., Mani N., and Rosenstein J.M. Roles of the endogenous VEGF receptors flt-1 and flk-1 in astroglial and vascular remodeling after brain injury. Exp Neurol 212 (2008) 108-117
60. Neary J.T., and Zimmermann H. Trophic functions of nucleotides in the central nervous system. Trends Neurosci 32 (2009) 189-198
61. Trincavelli M.L., Marroni M., Tuscano D., Ceruti S., Mazzola A., Mitro N., et al. Regulation of A2B adenosine receptor functioning by tumour necrosis factor a in human astroglial cells. J Neurochem 91 (2004) 1180-1190
62. Levison S.W., Jiang F.J., Stoltzfus O.K., and Ducceschi M.H. IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation. Glia 32 (2000) 328-337
63. Smith G.M., and Strunz C. Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes. Glia 52 (2005) 209-218
64. Flower D.R., North A.C.T., and Sansom C.E. The lipocalin protein family: structural and sequence overview. Biochim Biophys Acta 1482 (2000) 9-24
65. Lee S., Park J.Y., Lee W.H., Kim H., Park H.C., Mori K., et al. Lipocalin-2 is an autocrine mediator of reactive astrocytosis. J Neurosci 29 (2009) 234-249
66. Tsang M.C., Lo A.C., Cheung P.T., Chung S.S., and Chung S.K. Perinatal hypoxia-/ischemia-induced endothelin-1 mRNA in astrocyte-like and endothelial cells. NeuroReport 12 (2001) 2265-2270
67. Gadea A., Schinelli S., and Gallo V. Endothelin-1 regulates astrocyte proliferation and reactive gliosis via a JNK/c-Jun signaling pathway. J Neurosci 28 (2008) 2394-2408
68. B receptor agonist increases expression of tissue inhibitor of matrix metalloproteinase-1 and -3 in rat brain. Neuroscience 147 (2007) 620-630
69. Robel S, Mori T, Zoubaa S, Schlegel J, Sirko S, Faissner A, et al. Conditional deletion of beta1 integrin in astroglia causes partial reactive gliosis. Glia 2009; in press, doi:10.1002/glia.20876.
70. Goldshmit Y., McLenachan S., and Turnley A. Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Rev 52 (2006) 327-345
71. Bundesen L.Q., Scheel T.A., Bregman B.S., and Kromer L.F. Ephrin-B2 and EphB2 regulation of astrocyte meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci 23 (2003) 7789-7800
72. Fraser M.M., Zhu X., Kwon C.H., Uhlmann E.J., Gutmann D.H., and Baker S.J. Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo. Cancer Res 64 (2004) 7773-7779
73. Ma X.M., and Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10 (2009) 307-318
74. Chen C.J., Liao S.L., Huang Y.S., and Chiang A.N. RhoA inactivation is crucial to manganese-induced astrocyte stellation. Biochem Biophys Res Commun 326 (2005) 873-879
75. Etienne-Manneville S., and Hall A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCζ. Cell 106 (2001) 489-498
76. John G.R., Chen L., Rivieccio M.A., Melendez-Vasquez C.V., Hartley A., and Brosnan C.F. Interleukin-1beta induces a reactive astroglial phenotype via deactivation of the Rho GTPase-Rock axis. J Neurosci 24 (2004) 2837-2845
77. Burgos M., Calvo S., Molina F., Vaquero C.F., Samarel A., Llopis J., et al. PKCepsilon induces astrocyte stellation by modulating multiple cytoskeletal proteins and interacting with Rho A signalling pathways: implications for neuroinflammation. Eur J Neurosci 25 (2007) 1069-1078
78. Neary J.T., and Kang Y. Signaling from P2 nucleotide receptors to protein kinase cascades induced by CNS injury: implications for reactive gliosis and neurodegeneration. Mol Neurobiol 31 (2005) 95-103
79. Carbonell W.S., and Mandell J.W. Transient neuronal but persistent astroglial activation of ERK/MAP kinase after focal brain injury in mice. J Neurotrauma 20 (2003) 327-336
80. Heffron D.S., and Mandell J.W. Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension. Mol Cell Neurosci 28 (2005) 779-790
81. Franke H., Sauer C., Rudolph C., Krügel U., Hengstler J.G., and Illes P. P2 receptor-mediated stimulation of the PI3-K/Akt-pathway in vivo. Glia 57 (2009) 1031-1045
82. Aaronson D.S., and Horvath C.M. A road map for those who don't know JAK-STAT. Science 296 (2002) 1653-1655
83. Justicia C., Gabriel C., and Planas A.M. Activation of the JAK/STAT pathway following transient focal cerebral ischemia: signaling through Jak1 and Stat3 in astrocytes. Glia 30 (2000) 253-270
84. Sriram K., Benkovic S.A., Hebert M.A., Miller D.B., and O'Callaghan J.P. Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo?. J Biol Chem 279 (2004) 19936-19947
85. Xia X.G., Hofmann H.D., Deller T., and Kirsch M. Induction of STAT3 signaling in activated astrocytes and sprouting septal neurons following entorhinal cortex lesion in adult rats. Mol Cell Neurosci 21 (2002) 379-392
86. Okada S., Nakamura M., Katoh H., Miyao T., Shimazaki T., Ishii K., et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 12 (2006) 829-834
87. Herrmann J.E., Imura T., Song B., Qi J., Ao Y., Nguyen T.K., et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28 (2008) 7231-7243
88. Qin H., Niyongere S.A., Lee S.J., Baker B.J., and Benveniste E.N. Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes. J Immunol 181 (2008) 3167-3176
89. Choi JS, Shin YJ, Lee JY, Choi JY, Cha JH, Chun MH, et al. Enhanced expression of SOCS-2 in the rat hippocampus following transient forebrain ischemia. J Neurotrauma 2009; in press, doi:10.1089/neu.2008-0793.
90. Kubo M., Hanada T., and Yoshimura A. Suppressors of cytokine signaling and immunity. Nat Immunol 4 (2003) 1169-1176
91. Buffo A., Vosko M.R., Ertürk D., Hamann G.F., Jucker M., Rowitch D., et al. Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair. Proc Natl Acad Sci USA 102 (2005) 18183-18188
92. Tatsumi K., Takebayashi H., Manabe T., Tanaka K.F., Makinodan M., Yamauchi T., et al. Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes. J Neurosci Res 86 (2008) 3494-3502
93. Magnus T., Coksaygan T., Korn T., Xue H., Arumugam T.V., Mughal M.R., et al. Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced differentiation of glial precursors to astrocytes. J Neurosci Res 85 (2007) 2126-2137
94. + progenitors after acute brain injury: intracellular localization of oligodendrocyte transcription factor 2 is associated with their fate choice. Eur J Neurosci 29 (2009) 1853-1869
95. Chen Y., Miles D.K., Hoang T., Shi J., Hurlock E., Kernie S.G., et al. The basic helix-loop-helix transcription factor Olig2 is critical for reactive astrocyte proliferation after cortical injury. J Neurosci 28 (2008) 10983-10989
96. Hack M.A., Sugimori M., Lundberg C., Nakafuku M., and Götz M. Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6. Mol Cell Neurosci 25 (2004) 664-678
97. Moynagh P.N. The NF-kB pathway. J Cell Sci 118 (2005) 4589-4592
98. Brambilla R., Bracchi-Ricard V., Hu W.H., Frydel B., Bramwell A., Karmally S., et al. Inhibition of astroglial nuclear factor k B reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 202 (2005) 145-156
99. Khorooshi R., Babcock A.A., and Owens T. NF-kB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury. J Immunol 181 (2008) 7284-7291
100. Fernandez S., Fernandez A.M., Lopez-Lopez C., and Torres-Aleman I. Emerging roles of insulin-like growth factor-I in the adult brain. Growth Horm IGF Res 17 (2007) 89-95
101. Pérez-Ortiz J.M., Serrano-Pérez M.C., Pastor M.D., Martín E.D., Calvo S., Rincón M., et al. Mechanical lesion activates newly identified NFATc1 in primary astrocytes: implication of ATP and purinergic receptors. Eur J Neurosci 27 (2008) 2453-2465
102. Sama M.A., Mathis D.M., Furman J.L., Abdul H.M., Artiushin I.A., Kraner S.D., et al. Interleukin-1β-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity. J Biol Chem 283 (2008) 21953-21964
103. Zawadzka M., and Kaminska B. A novel mechanism of FK506-mediated neuroprotection: downregulation of cytokine expression in glial cells. Glia 49 (2005) 36-51
104. Ramon y Cajal S. In: DeFelipe J., and Jones E.G. (Eds). Degeneration and regeneration of the nervous system 46 (1928), Oxford Univ. Press, London 465-476 May R, trans., Res; 1991 (reprint)
105. Liuzzi F.J., and Lasek R.J. Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway. Science 237 (1987) 642-645
106. Davies S.J., Fitch M.T., Memberg S.P., Hall A.K., Raisman G., and Silver J. Regeneration of adult axons in white matter tracts of the central nervous system. Nature 390 (1997) 680-683
107. Crespo D., Asher R.A., Lin R., Rhodes K.E., and Fawcett J.W. How does chondroitinase promote functional recovery in the damaged CNS?. Exp Neurol 206 (2007) 159-171
108. Hagino S., Iseki K., Mori T., Zhang Y., Hikake T., Yokoya S., et al. Slit and glypican-1 mRNAs are coexpressed in the reactive astrocytes of the injured adult brain. Glia 42 (2003) 130-138
109. Niclou S.P., Franssen E.H., Ehlert E.M., Taniguchi M., and Verhaagen J. Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth. Mol Cell Neurosci 24 (2003) 902-912
110. Apostolova I., Irintchev A., and Schachner M. Tenascin-R restricts posttraumatic remodeling of motoneuron innervation and functional recovery after spinal cord injury in adult mice. J Neurosci 26 (2006) 7849-7859
111. Li L., Lundkvist A., Andersson D., Wilhelmsson U., Nagai N., Pardo A.C., et al. Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab 28 (2008) 468-481
112. Rossi D., Brady J., and Mohr C. Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10 (2007) 1377-1386
113. Contreras J.E., Sánchez H.A., Véliz L.P., Bukauskas F.F., Bennett M.V.L., and Sáez J.C. Role of connexin-based gap junction channels and hemichannels in ischemia-induced cell death in nervous tissue. Brain Res Brain Res Rev 47 (2004) 290-303
114. Neumann H., Schweigreiter R., Yamashita T., Rosenkranz K., Wekerle H., and Barde Y.A. Tumor necrosis factor inhibits neurite outgrowth and branching of hippocampal neurons by a rho-dependent mechanism. J Neurosci 22 (2002) 854-862
115. D'Souza S.D., Alinauskas K.A., and Antel J.P. Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factor-mediated injury. J Neurosci Res 43 (1996) 289-298
116. Williams A., Piaton G., and Lubetzki C. Astrocytes-friends or foes in multiple sclerosis?. Glia 55 (2007) 1300-1312
117. Dubois B., Opdenakker G., Carton H., and Gelatinase. B in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neurol Belg 99 (1999) 53-56
118. Williams A., Piaton G., Aigrot M.S., Belhadi A., Theaudin M., Petermann F., et al. Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis?. Brain 130 (2007) 2554-2565
119. Cheng X., Wang Y., He Q., Qiu M., Whittemore S.R., and Cao Q. Bone morphogenetic protein signaling and olig1/2 interact to regulate the differentiation and maturation of adult oligodendrocyte precursor cells. Stem Cells 25 (2007) 3204-3214
120. Hsu J.Y., Bourguignon L.Y., Adams C.M., Peyrollier K., Zhang H., Fandel T., et al. Matrix metalloproteinase-9 facilitates glial scar formation in the injured spinal cord. J Neurosci 28 (2008) 13467-13477
121. Zhao B.Q., Wang S., Kim H.Y., Storrie H., Rosen B.R., Mooney D.J., et al. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med 12 (2006) 441-445
122. Brambilla R., Hurtado A., Persaud T., Esham K., Pearse D.D., Oudega M., et al. Transgenic inhibition of astroglial NFkappaB leads to increased axonal sparing and sprouting following spinal cord injury. J Neurochem 110 (2009) 765-778
123. Erschbamer M., Pernold K., and Olson L. Inhibiting epidermal growth factor receptor improves structural, locomotor, sensory, and bladder recovery from experimental spinal cord injury. J Neurosci 27 (2007) 6428-6435
124. Liu B., and Neufeld A.H. Activation of epidermal growth factor receptors directs astrocytes to organize in a network surrounding axons in the developing rat optic nerve. Dev Biol 273 (2004) 297-307
125. Rolls A., Shechter R., and Schwartz M. The bright side of the glial scar in CNS repair. Nat Rev Neurosci 10 (2009) 235-241
126. Danbolt N.C. Glutamate uptake. Prog Neurobiol 65 (2001) 1-105
127. Ottersen O.P., Laake J.H., Reichelt W., Haug F.M., and Torp R. Ischemic disruption of glutamate homeostasis in brain: quantitative immunocytochemical analyses. J Chem Neuroanat 12 (1996) 1-14
128. Rao V.L., Dogan A., Todd K.G., Bowen K.K., Kim B.T., Rothstein J.D., et al. Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain. J Neurosci 21 (2001) 1876-1883
129. Escartin C., Brouillet E., Gubellini P., Trioulier Y., Jacquard C., Smadja C., et al. Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo. J Neurosci 26 (2006) 5978-5989
130. Gorovits R., Avidan N., Avisar N., Shaked I., and Vardimon L. Glutamine synthetase protects against neuronal degeneration in injured retinal tissue. Proc Natl Acad Sci USA 94 (1997) 7024-7029
131. Kazazoglou T., Fleischer-Lambropoulos E., Geladopoulos T., Kentroti S., Stefanis C., and Vernadakis A. Differential responsiveness of late passage C-6 glial cells and advanced passages of astrocytes derived from aged mouse cerebral hemispheres to cytokines and growth factors: glutamine synthetase activity. Neurochem Res 21 (1996) 609-614
132. Brown A.M. Brain glycogen re-awakened. J Neurochem 89 (2004) 537-552
133. Phillis J.W., and O'Regan M.H. A potentially critical role of phospholipases in central nervous system ischemic, traumatic, and neurodegenerative disorders. Brain Res Brain Res Rev 44 (2004) 13-47
134. Gavillet M., Allaman I., and Magistretti P.J. Modulation of astrocytic metabolic phenotype by proinflammatory cytokines. Glia 56 (2008) 975-989
135. Dringen R., Gutterer J.M., and Hirrlinger J. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267 (2000) 4912-4916
136. Rosenstein J.M., and Krum J.M. New roles for VEGF in nervous tissue-beyond blood vessels. Exp Neurol 187 (2004) 246-253
137. Argaw A.T., Gurfein B.T., Zhang Y., Zameer A., and John G.R. VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci USA 106 (2009) 1977-1982
138. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 438 (2005) 932-936
139. Bush T.G., Puvanachandra N., Horner C.H., Polito A., Ostenfeld T., Svendsen C.N., et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23 (1999) 297-308
140. Faulkner J.R., Herrmann J.E., Woo M.J., Tansey K.E., Doan N.B., and Sofroniew M.V. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24 (2004) 2143-2155
141. Wang Y., Moges H., Bharucha Y., and Symes A. Smad3 null mice display more rapid wound closure and reduced scar formation after a stab wound to the cerebral cortex. Exp Neurol 203 (2007) 168-184
142. Saadoun S., Papadopoulos M.C., Watanabe H., Yan D., Manley G.T., and Verkman A.S. Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J Cell Sci 118 (2005) 5691-5698
143. Lee S.W., Kim W.J., Choi Y.K., Song H.S., Son M.J., Gelman I.H., et al. SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier. Nat Med 9 (2003) 900-906
144. Tran M.D., Wanner I.B., and Neary J.T. Purinergic receptor signaling regulates N-cadherin expression in primary astrocyte cultures. J Neurochem 105 (2008) 272-286
145. Morel M.P., Dusart I., and Sotelo C. Sprouting of adult Purkinje cell axons inlesioned mouse cerebellum: "non-permissive" versus "permissive" environment. J Neurocytol 31 (2002) 633-647
146. Merkle F.T., and Alvarez-Buylla A. Neural stem cells in mammalian development. Curr Opin Cell Biol 18 (2006) 704-709
147. Malatesta P., Hack M.A., Hartfuss E., Kettenmann H., Klinkert W., Kirchhoff F., et al. Neuronal or glial progeny: regional differences in radial glia fate. Neuron 37 (2003) 751-764
148. Doetsch F., García-Verdugo J.M., and Alvarez-Buylla A. Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci USA 96 (1999) 11619-11624
149. Seri B., García-Verdugo J.M., McEwen B.S., and Alvarez-Buylla A. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21 (2001) 7153-7160
150. Pixley S.K., and de Vellis J. Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Brain Res 317 (1984) 201-209
151. Mori T., Buffo A., and Götz M. The novel roles of glial cells revisited: the contribution of radial glia and astrocytes to neurogenesis. Curr Top Dev Biol 69 (2005) 67-99
152. Berninger B., Costa M.R., Koch U., Schroeder T., Sutor B., Grothe B., et al. Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia. J Neurosci 27 (2007) 8654-8664
153. Laywell E.D., Rakic P., Kukekov V.G., Holland E.C., and Steindler D.A. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc Natl Acad Sci USA 97 (2000) 13883-13888
154. Ohori Y., Yamamoto S., Nagao M., Sugimori M., Yamamoto N., Nakamura K., et al. Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord. J Neurosci 26 (2006) 11948-11960
155. Sellers D.L., Maris D.O., and Horner P.J. Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury. J Neurosci 29 (2009) 6722-6733
156. Munoz L., Ranaivo H., Roy S.M., Hu W., Craft J.M., McNamara L.K., et al. A novel p38alpha MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model. J Neuroinflammation 4 (2007) 21
157. Brines M., and Cerami A. Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci 6 (2005) 484-494
158. Gunnarson E., Song Y., Kowalewski J.M., Brismar H., Brines M., Cerami A., et al. Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection. Proc Natl Acad Sci USA 106 (2009) 1602-1607
159. White R.E., Yin F.Q., and Jakeman L.B. TGF-alpha increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice. Exp Neurol 214 (2008) 10-24
160. Palma V., Lim D.A., Dahmane N., Sanchez P., Brionne T.C., Herzberg C.D., et al. Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 132 (2005) 335-344
161. Jiao J., and Chen D.F. Induction of neurogenesis in nonconventional neurogenic regions of the adult central nervous system by niche astrocyte-produced signals. Stem Cells 26 (2008) 1221-1230
162. Colak D., Mori T., Brill M.S., Pfeifer A., Falk S., Deng C., et al. Adult neurogenesis requires smad4-mediated bone morphogenic protein signaling in stem cells. J Neurosci 28 (2008) 434-446
163. Hampton D.W., Asher R.A., Kondo T., Steeves J.D., Ramer M.S., and Fawcett J.W. A potential role for bone morphogenetic protein signalling in glial cell fate determination following adult central nervous system injury in vivo. Eur J Neurosci 26 (2007) 3024-3035
164. Chen J., Leong S.Y., and Schachner M. Differential expression of cell fate determinants in neurons and glial cells of adult mouse spinal cord after compression injury. Eur J Neurosci 22 (2005) 1895-1906
165. Yamamoto S., Nagao M., Sugimori M., Kosako H., Nakatomi H., Yamamoto N., et al. Transcription factor expression and notch-dependent regulation of neural progenitors in the adult rat spinal cord. J Neurosci 21 (2001) 9814-9823
166. Arumugam T.V., Chan S.L., Jo D.G., Yilmaz G., Tang S.C., Cheng A., et al. Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat Med 12 (2006) 621-623
167. Fernandez A.M., Fernandez S., Carrero P., Garcia-Garcia M., and Torres-Aleman I. Calcineurin in reactive astrocytes plays a key role in the interplay between pro-inflammatory and anti-inflammatory signals. J Neurosci 27 (2007) 8745-8756
168. Atkinson P.J., Dellovade T., Albers A., Von Schack D., Saraf K., Needle E., et al. Sonic Hedgehog signaling in astrocytes is dependent on p38 mitogen-activated protein kinase and G-protein receptor kinase 2. J Neurochem 108 (2009) 1539-1549